7202
J . Org. Chem. 1996, 61, 7202-7206
P r ep a r a tion of γ,δ-Un sa tu r a ted
â-Ketop h osp h on a tes fr om Ter tia r y
r-Allen ic Alcoh ols. Th e Syn th esis of
(()-(E)-r-Atla n ton e
Richard W. Friesen and Marc Blouin*
Department of Medicinal Chemistry, Merck Frosst Centre
for Therapeutic Research, P. O. Box 1005, Pointe-Claire -
Dorval, Que´bec, Canada, H9R 4P8
Received May 15, 1996
In tr od u ction
â-Ketophosphonates have been shown to be valuable
synthetic intermediates for the preparation of R,â-
unsaturated carbonyl compounds via the Horner-Wads-
worth-Emmons (“HWE”) reaction.1 Such a reaction of
γ,δ-unsaturated â-ketophosphonates 1 (or 2-oxo-3-alken-
ylphosphonates) with carbonyl compounds provides ac-
It is possible for γ,δ-unsaturated â-ketophosphonates
to be involved in other chemical tranformations, since one
can view them as phosphorus-stabilized enones. In a
series of very interesting reports, Wada and Kanemasa
described their use as heterodienes in an inverse electron-
demand Diels-Alder reaction with vinyl ethers, giving
rise to 2-alkoxy-6-(phosphinylmethyl)-3,4-dihydro-2H-
pyran derivatives.7 They have also shown that these
alkenylphosphonates can serve as Michael acceptors in
reactions with carbonyl-stabilized carbanions (i.e. derived
from â-keto esters, â-diketones or R-sulfonyl ketones)
producing 2-cyclohexen-1-ones.8 Silyl enol ethers also act
as Michael donors with this type of phosphonate, to afford
either 2-cyclohexen-1-ones8,9 or 2-phosphinyl-2-cyclohexen-
1-ones,8 depending upon whether basic or acidic condi-
tions, respectively, are used. Simple modifications, like
reduction of the olefin moiety,10 reductive amination of
the carbonyl group,11 functionalization at the R-carbon,2a,c
or condensation with epoxides (to give R′-cyclopropylen-
ones)12 can also be performed on γ,δ-unsaturated â-ke-
tophosphonates.
A number of methods currently exist for the prepara-
tion of 2-oxo-3-alkenylphosphonates.13 Aside from a few
exceptions,13f-h,j these reactions are the same as those
that are employed for the preparation of saturated
â-ketophosphonates and are based on the acylation of
alkylphosphonate anions with R,â-unsaturated carboxylic
acid derivatives (i.e. acid chlorides and esters).13a-d
Surprisingly, as far as we are aware, there are no reports
on the preparation of γ,δ-unsaturated â-ketophospho-
nates by the commonly used Arbuzov reaction14 between
a trialkyl phosphite and an R-haloenone. In spite of its
cess to R,R′-divinyl ketones (or R,R′-dienones) 2.2
A
Nazarov cyclization3 converts these cross-conjugated
ketones4 into the useful and widely encountered 2-cyclo-
pentenone unit 3.5 The R,R′-divinyl ketone moiety is also
present in a number of terpenoid natural products.6
R-Atlantone (4)6e,f and â-damascone (5)6d are two such
examples.
(1) For reviews on the Horner-Wadsworth-Emmons reaction,
including syntheses and applications of â-ketophosphonates, see: (a)
Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863. (b) Wadsworth,
W. S., J r. Org. React. 1977, 25, 73. (c) Boutagy, J .; Thomas, R. Chem.
Rev. 1974, 74, 87.
(2) (a) Minami, T.; Nakayama, M.; Fujimoto, K.; Matsuo, S. J . Chem.
Soc., Chem. Commun. 1992, 190. (b) Motoyoshiya, J .; Yazaki, T.;
Hayashi, S. J . Org. Chem. 1991, 56, 735. (c) Mikolajczyk, M.; Zura-
winski, R. Synlett 1991, 575. (d) Kodama, M.; Shiobara, Y.; Sumitomo,
H.; Mitani, K.; Ueno, K. Chem. Pharm. Bull. 1987, 35, 4039. (e) Sakai,
T.; Amano, E.; Miyata, K.; Utaka, M.; Takeda, A. Bull. Chem. Soc.
J pn. 1987, 60, 1945. (f) Motoyoshiya, J .; Miyajima, M.; Hirakawa, K.;
Kakurai, T. J . Org. Chem. 1985, 50, 1326.
(3) For reviews, see: (a) Denmark, S. E. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford,
1991; Vol. 5, pp 751-784. (b) Santelli-Rouvier, C.; Santelli, M.
Synthesis 1983, 429. For some recent examples and applications, see:
(c) Kang, K.-T.; Kim, S. S.; Lee, J . C.; U, J . S. Tetrahedron Lett. 1992,
33, 3495. (d) Frank-Neumann, M.; Miesch, M.; Gross, L. Tetrahedron
Lett. 1992, 33, 3879. (e) Paquette, L. A.; Kang, H.-J . J . Am. Chem.
Soc. 1991, 113, 2610. (f) Andrews, J . F. P.; Regan, A. C. Tetrahedron
Lett. 1991, 32, 7731. (g) Yamazaki, S.; Mizuno, W.; Yamabe, S. J . Chem.
Soc., Perkin Trans. 1 1991, 1555. (h) See also refs 2a,b.
(4) For some selected examples of other reactions of cross-conjugated
ketones, see: (a) Krein, E. B.; Aizenshtat, Z. J . Org. Chem. 1993, 58,
6103. (b) Chiacchio, U.; Corsaro, A.; Rescifina, A.; Testa, M. G.;
Purrello, G. Heterocycles 1993, 36, 223. (c) Nakamura, E.; Kubota, K.;
Isaka, M. J . Org. Chem. 1992, 57, 5809. (d) Hitchcock, S. A.; Pattenden,
G. Tetrahedron Lett. 1992, 33, 4843. (e) Grigg, R.; Kennewell, P.; Savic,
V.; Sridharan, V. Tetrahedron 1992, 48, 10423. (f) Yamaguchi, M.;
Hayashi, A.; Hirama, M. Chem. Lett. 1992, 2479. (g) Diaz, E.; Barrios,
H.; Toscano, R. A.; Yuste, F.; Reynolds, W. F.; Aguilera, J . L.; Caballero,
E. J . Heterocycl. Chem. 1992, 29, 1325. (h) Hagiwara, H.; Okano, A.;
Uda, H. J . Chem. Soc., Perkin Trans. 1 1990, 2109. (i) Richter, F.; Otto,
H.-H. Liebigs Ann. Chem. 1990, 7. (j) Richter, F.; Otto, H.-H.
Tetrahedron Lett. 1985, 26, 4351. (k) Britten-Kelly, M.; Willis, B. J .
Synthesis 1980, 27.
(7) (a) Wada, E.; Kanemasa, S.; Tsuge, O. Chem. Lett. 1989, 675.
(b) Wada, E.; Kanemasa, S.; Tsuge, O. Bull. Chem. Soc. J pn. 1989,
62, 1198. (c) Wada, E.; Kanemasa, S.; Tsuge, O. Bull. Chem. Soc. J pn.
1989, 62, 860.
(8) Wada, E.; Funakoshi, J .; Kanemasa, S. Bull. Chem. Soc. J pn.
1992, 65, 2456.
(9) Kuo, F.; Fuchs, P. L. Synth. Commun. 1986, 16, 1745.
(10) Hanessian, S.; Rancourt, G.; Guindon, Y. Can. J . Chem. 1978,
56, 1843.
(11) Varlet, J . M.; Collignon, N.; Savignac, P. Tetrahedron 1981, 37,
3713.
(5) (a) Tolstikov, G. A.; Miftakhov, M. S.; Danilova, N. A.; Vel’der,
Ya. L.; Spirikhin, L. V. Synthesis 1989, 625. (b) Hudlicky, T.; Price, J .
D. Chem. Rev. 1989, 89, 1467. (c) Ramaiah, M. Synthesis 1984, 529.
(d) Ellison, R. A. Synthesis 1973, 397. (e) See also refs 3a, Section 6.3.8,
and 3b, Section 8.
(6) (a) Matthes, H. W. D.; Luu, B.; Ourrisson, G. Phytochemistry
1980, 19, 2643. (b) Kalsi, P. S.; Chhabra, B. R.; Singh, O. S. Experientia
1979, 35, 481. (c) Kalsi, P. S.; Singh, O. S.; Chhabra, B. R. Phytochem-
istry 1978, 17, 576. (d) Snowden, R. L.; Linder, S. M.; Muller, B. L.;
Schulte-Elte, K. H. Helv. Chim. Acta 1987, 70, 1858 and refs cited
therein. (e) Pfau, von A. S.; Plattner, P. Helv. Chim. Acta 1934, 17,
129. (f) Pande, B. S.; Krishnappa, S.; Bisarya, S. C.; Dev, S. Tetrahe-
dron 1971, 27, 841. (g) de Villiers, D. J . J .; Garbers, C. F.; Laurie, R.
N. Phytochemisry 1971, 10, 1359. (h) J ung, J . H.; Chang, C.-J .; Smith,
D. L.; McLaughlin, J . L.; Pummangura, S.; Chaichantipyuth, C.;
Patarapanich, C. J . Nat. Prod. 1991, 54, 500.
(12) J acks, T. E.; Nibbe, H.; Wiemer, D. F. J . Org. Chem. 1993, 58,
4584.
(13) For reactions of alkylphosphonate anions with R,â-unsaturated
carboxylic acid chlorides and/or esters, see: (a) Corey, E. J .; Ohuchida,
S.; Hahl, R. J . Am. Chem. Soc. 1984, 106, 3875. (b) Mathey, F.;
Savignac, P. Tetrahedron 1978, 34, 649. (c) Aboujaoude, E. E.;
Collignon, N.; Teulade, M.-P.; Savignac, P. Phosphorus Sulfur 1985,
25, 57. (d) See also refs 2b-d,f. For other methods of preparation, see:
(e) Koh, Y. J .; Oh, D. Y. Tetrahedron Lett. 1993, 34, 2147. (f) Tsuge,
O.; Kanemasa, S.; Suga, H.; Nakagawa, N. Bull. Chem. Soc. J pn. 1987,
60, 2463. (g) Peiffer, G.; Courbis, P. Can. J . Chem. 1974, 52, 2894. (h)
See also refs 2e, 7c, and 8. For examples with γ,δ-unsaturation within
a carbocycle, see: (i) An, Y.-Z.; An, J . G.; Wiemer, D. F. J . Org. Chem.
1994, 59, 8197 and refs cited therein. (j) Castagnino, E.; D’Auria, M.;
De Mico, A.; D’Onofrio, F.; Piancatelli, G. J . Chem. Soc., Chem.
Commun. 1987, 907. (k) See also ref 12 and refs cited therein.
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